Volume 15 Issue 2, February 2014

To regulate gene expression, transcription factors must access DNA, which is organized in chromatin. This occurs on many timescales; in this Review, the authors discuss the mechanisms that underlie this interaction in regulated and stochastic processes.

The derivation of disease-relevant cell types from pluripotent stem cells holds much promise for disease therapy. The recent progress in directed differentiation and the challenges ahead are discussed in this Review.

This Review describes the diverse roles for histone-modifying and chromatin-remodelling enzymes in mammalian differentiation. These enzymes are involved in both maintaining pluripotency and specifying cell lineage commitment. Recent progress includes their functional characterization in mouse modelsin vivoand a new appreciation of their multifaceted molecular functions.

Constraint-based modelling methods systematize biochemical, genetic and genomic knowledge into a mathematical framework, which enables a mechanistic description of metabolic physiology. Recent successes in using this approach have implications for microbial evolution, interaction networks, genetic engineering and drug discovery.

Methods that are based on next-generation sequencing technology are used for a range of applications from genome sequencing to transcriptomic and epigenomic studies. Here, the authors discuss the important issue of sequencing depth in the design of such experiments.

In the past few years, there have been rapid advances in the identification of the genetic components of autism spectrum disorders, particularly in the form ofde novomutations. Here, the authors review these developments in light of genetic models for autism spectrum disorders.